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@article{Ho:2023:10.1038/s41586-023-05948-2,
author = {Ho, A and Orton, R and Tayler, R and Asamaphan, P and Herder, V and Davis, C and Tong, L and Smollett, K and Manali, M and Allan, J and Rawlik, K and McDonald, SE and Vink, E and Pollock, L and Gannon, L and Evans, C and McMenamin, J and Roy, K and Marsh, K and Divala, T and Holden, MTG and Lockhart, M and Yirrell, D and Currie, S and O'Leary, M and Henderson, D and Shepherd, SJ and Jackson, C and Gunson, R and MacLean, A and McInnes, N and Bradley-Stewart, A and Battle, R and Hollenbach, JA and Henderson, P and Odam, M and Chikowore, P and Oosthuyzen, W and Chand, M and Hamilton, MS and Estrada-Rivadeneyra, D and Levin, M and Avramidis, N and Pairo-Castineira, E and Vitart, V and Wilkie, C and DIAMONDS, Consortium and ISARIC4C, Investigators and Palmarini, M and Ray, S and Robertson, DL and da, Silva Filipe A and Willett, BJ and Breuer, J and Semple, MG and Turner, D and Baillie, JK and Thomson, EC},
doi = {10.1038/s41586-023-05948-2},
journal = {Nature},
pages = {555--563},
title = {Adeno-associated virus 2 infection in children with non-A-E hepatitis.},
url = {http://dx.doi.org/10.1038/s41586-023-05948-2},
volume = {617},
year = {2023}
}

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TY  - JOUR
AB  - An outbreak of acute hepatitis of unknown aetiology in children was reported in Scotland1 in April 2022 and has now been identified in 35 countries2. Several recent studies have suggested an association with human adenovirus with this outbreak, a virus not commonly associated with hepatitis. Here we report a detailed case-control investigation and find an association between adeno-associated virus 2 (AAV2) infection and host genetics in disease susceptibility. Using next-generation sequencing, PCR with reverse transcription, serology and in situ hybridization, we detected recent infection with AAV2 in plasma and liver samples in 26 out of 32 (81%) cases of hepatitis compared with 5 out of 74 (7%) of samples from unaffected individuals. Furthermore, AAV2 was detected within ballooned hepatocytes alongside a prominent T cell infiltrate in liver biopsy samples. In keeping with a CD4+ T-cell-mediated immune pathology, the human leukocyte antigen (HLA) class II HLA-DRB104:01 allele was identified in 25 out of 27 cases (93%) compared with a background frequency of 10 out of 64 (16%; P = 5.49 × 10-12). In summary, we report an outbreak of acute paediatric hepatitis associated with AAV2 infection (most likely acquired as a co-infection with human adenovirus that is usually required as a 'helper virus' to support AAV2 replication) and disease susceptibility related to HLA class II status.
AU  - Ho,A
AU  - Orton,R
AU  - Tayler,R
AU  - Asamaphan,P
AU  - Herder,V
AU  - Davis,C
AU  - Tong,L
AU  - Smollett,K
AU  - Manali,M
AU  - Allan,J
AU  - Rawlik,K
AU  - McDonald,SE
AU  - Vink,E
AU  - Pollock,L
AU  - Gannon,L
AU  - Evans,C
AU  - McMenamin,J
AU  - Roy,K
AU  - Marsh,K
AU  - Divala,T
AU  - Holden,MTG
AU  - Lockhart,M
AU  - Yirrell,D
AU  - Currie,S
AU  - O'Leary,M
AU  - Henderson,D
AU  - Shepherd,SJ
AU  - Jackson,C
AU  - Gunson,R
AU  - MacLean,A
AU  - McInnes,N
AU  - Bradley-Stewart,A
AU  - Battle,R
AU  - Hollenbach,JA
AU  - Henderson,P
AU  - Odam,M
AU  - Chikowore,P
AU  - Oosthuyzen,W
AU  - Chand,M
AU  - Hamilton,MS
AU  - Estrada-Rivadeneyra,D
AU  - Levin,M
AU  - Avramidis,N
AU  - Pairo-Castineira,E
AU  - Vitart,V
AU  - Wilkie,C
AU  - DIAMONDS,Consortium
AU  - ISARIC4C,Investigators
AU  - Palmarini,M
AU  - Ray,S
AU  - Robertson,DL
AU  - da,Silva Filipe A
AU  - Willett,BJ
AU  - Breuer,J
AU  - Semple,MG
AU  - Turner,D
AU  - Baillie,JK
AU  - Thomson,EC
DO  - 10.1038/s41586-023-05948-2
EP  - 563
PY  - 2023///
SP  - 555
TI  - Adeno-associated virus 2 infection in children with non-A-E hepatitis.
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-023-05948-2
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36996873
VL  - 617
ER  -

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